Fig. 1

The relationship between mTOR and tumors. Overactivation of mTORC1 can promote tumor formation, proliferation, and metastasis, while mTORC2 can regulate the expression of mTORC1 through the mTORC2/AKT/TSC/Rehb pathway. Pathway 1: The extracellular growth signals and intracellular LKB1 mutations activate mTORC1, which reduces the ubiquitination of histone H2A and H2A after DNA damage by phosphorylating RNF168. This can lead to damage to DNA repair and promote the formation of tumors. Pathway 2: The ubiquitination of Rheb reduces Rheb activity by promoting Rheb binding to TSC2. The down-regulation of Rehb reduces the activation of mTORC1, leading to the inhibition of tumor growth. Pathway 3: TRAF2 and Otud7B respectively regulate mTORC1/2 activity by up-regulating or down-regulating the ubiquitination level of G beta L of mTORC2. TRAF2 enhanced the activity of mTORC1 and inhibited the activity of mTORC2. Although down-regulation of mTORC2 expression inactivates the AKT/TSC/Rehb/mTORC1 pathway, overall mTORC1 activity is enhanced. However, Otud7B has the opposite effect on TRAF2. Pathway 4: Mutated Ras binds mTOR and MAPKAP1 of mTORC2 to promote mTORC2 expression. The up-regulation of mTORC2 promotes tumor proliferation through the AKT/TSC/Rehb/mTORC1 pathway. Pathway 5: Deletion of the PTEN gene induces the expression of B7-H1 to increase tumor progression and invasion. Pathway 6: The PI3K/PTEN/AKT/mTOR pathway is involved in the invasion and metastasis of liver cancer by up-regulating MMP-9